Phase 3
Completed N=19
A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)
Graft vs Host Disease
Source: ClinicalTrials.gov NCT03474679 ↗
Enrolled (actual)
19
Serious AEs
63.2%
Results posted
Feb 2023
Primary outcomePrimary: Overall Response Rate (ORR) — 84.2 Percentage of participants
◆ Published Evidence
Established
33citations · ~7 / year
An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease.
Summary
The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).
Linked Publications (2)
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An Open-Label, Single-Arm, Multicenter Study of Ibrutinib in Japanese Patients With Steroid-dependent/Refractory Chronic Graft-Versus-Host Disease.
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Long-term Use of Ibrutinib in Japanese Patients with Steroid Dependent/Refractory cGVHD: Final Analysis of Multicenter Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) |
84.2 | — |
| SECONDARY Sustained Response Rate |
68.8 | — |
| SECONDARY Duration of Response (DOR) |
NA | — |
| SECONDARY cGVHD Response Rate at Each Timepoints |
26.3; 42.1; 52.6; 47.4; 47.4; 42.1 | — |
| SECONDARY Change in the Amount of Corticosteroid Required Over Time |
0.270; 0.250; 0.150; 0.140; 0.140 | — |
| SECONDARY Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score |
52.6 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
19 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib |
3683.7; 4024.8 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib |
2929.3; 4035.6 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Ibrutinib |
490.45; 478.01 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib |
3.87; 4.02 | — |
| SECONDARY Elimination Half-Life (t1/2) of Ibrutinib |
4.9; 4.4 | — |
| SECONDARY Apparent Clearance (CL/F) of Ibrutinib |
194211; 162457 | — |
| SECONDARY Apparent Volume of Distribution (Vd/F) of Ibrutinib |
1350160 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib |
2643.8; 2659.2 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227 |
1976.9; 2547.6 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227 |
1803.0; 2547.6 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of PCI-45227 |
185.37; 203.16 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227 |
4.00; 4.02 | — |
| SECONDARY Elimination Half-Life (t1/2) of PCI-45227 |
5.9; 5.4 | — |
| SECONDARY Apparent Clearance (CL/F) of PCI-45227 |
251681; 111922 | — |
| SECONDARY Apparent Volume of Distribution (Vd/F) of PCI-45227 |
2148283 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227 |
1766.1; 3752.6 | — |
Eligibility Criteria
Inclusion Criteria
- Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to ( =1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks
- Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib
- At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib
- Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
- Karnofsky or Lansky (participants less than [ =60
Exclusion Criteria
- Active acute graft versus host disease (GVHD)
- More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments
- History of treatment with a tyrosine kinase inhibitor (example [e.g.] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma
- History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib
Data sourced from ClinicalTrials.gov (NCT03474679) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.